• Rahul Raj, Jaakko Kaprio, Miikka Korja, Era D Mikkonen, Pekka Jousilahti, and Jari Siironen.
• Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
• PLoS Med. 2017 Jul 1; 14 (7): e1002316.

BackgroundPrevious epidemiological studies suggest that working-aged persons with a history of moderate-to-severe traumatic brain injury (TBI) may have an increased risk for developing neurodegenerative disease (NDD) while persons with a history of mild TBI do not. In this comprehensive nationwide study in Finland, we assessed the risk of NDD and history of moderate-to-severe TBI in the working-age population.Methods And FindingsWe performed a population-based follow-up study using the Finnish Care Register for Health Care to identify all persons between the ages of 18 and 65 years hospitalized during 1987-2014 due to TBI who did not have a baseline NDD diagnosis. We compared the risk of hospitalization with NDD between persons hospitalized due to moderate-to-severe TBI (intracranial lesions) and persons hospitalized due to mild TBI (no intracranial lesions). Follow-up NDD diagnoses were recorded from 1 year following the TBI to the end of 2014. NDD diagnoses included dementia, Parkinson disease, and amyotrophic lateral sclerosis. We used a Cox proportional hazards model, adjusting for age, sex, education, and socioeconomic group, to assess the association between TBI and NDD. In total, 19,936 and 20,703 persons with a history of moderate-to-severe TBI and mild TBI, respectively, were included. The overall time at risk was 453,079 person-years (median 10 years per person). In total, 3.5% (N = 696) persons in the moderate-to-severe TBI group developed NDD compared to 1.6% (N = 326) in the mild TBI group. After adjusting for covariates, moderate-to-severe TBI was associated with an increased risk for NDD, with a hazard ratio (HR) of 1.8 (95% CI 1.6-2.1) compared to mild TBI. Of the NDD subtypes, only moderate-to-severe TBI was associated with an increased risk for dementia (HR 1.9, 95% CI 1.6-2.2). Yet, this large-scale epidemiological study does not prove that there is a causal relationship between moderate-to-severe TBI and NDD. Further, the Care Register for Health Care includes only hospitalized persons; thus, patients diagnosed with NDD in the outpatient setting may have been missed. Additional limitations include the potential for miscoding and unmeasured confounds.ConclusionsIn working-aged persons, a history of moderate-to-severe TBI is associated with an increased risk for future dementia but not for Parkinson disease or amyotrophic lateral sclerosis.

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